LOCALIZED INTRAMURAL DRUG-DELIVERY DURING BALLOON ANGIOPLASTY USING HYDROGEL-COATED BALLOONS AND PRESSURE-AUGMENTED DIFFUSION

Objectives. This study was designed to assess the feasibility of using hydrogel-coated balloons to deliver biologically active agents to the blood vessel wall. Background. The local intramural delivery of therapeutic agents during balloon angioplasty has been proposed as an adjunctive technique for preventing early intracoronary thrombosis and late restenosis. Methods. To assess the efficacy of delivery and depth of penetration in vitro, local delivery of horseradish peroxidase was performed in 40 porcine peripheral arteries, and delivery of fluoresceinated heparin was performed in 20 porcine peripheral arteries and 7 human atheromatous arteries. To determine the persistence of these agents in the vessel wall in vivo, horseradish peroxidase was delivered to 18 porcine peripheral arteries that were harvested at intervals of 45 min to 48 h. Fluoresceinated heparin was delivered to 22 porcine peripheral arteries, 14 with the use of a protective sleeve, harvested at intervals of 30 s to 24 h. Results. In vitro agent delivery was successful in all specimens. The depth of penetration of horseradish peroxidase was directly related to both balloon pressure (p < 0.04) and duration of inflation (p < 0.01), In vivo peroxidase staining was evident at 45 and 90 min but not thereafter. With the use of a protective sleeve, heparin was present in all arteries harvested at 30 s, with marked dissipation at 1 and 24 h. Without a sleeve, no fluorescein staining was detected in any artery. With both agents, delivery occurred consistently over broad regions of the vessel wall that were free of architectural disruption. Conclusions. Hydrogel coated balloons can deliver biologically active agents to the vessel wall without gross tissue disruption and may provide an atraumatic method for the local delivery of therapeutic agents during balloon angioplasty.